Given the poor prognosis of HIV-associated non-Hodgkin's lymphoma (NHL) and it's still high incidence in HAART era, more intensive therapy is required in patients with initially severe stage of NHL or relapsing after first-line chemotherapy.

The purpose of this study is to evaluate the safety of an intensive chemotherapy followed by peripheral blood cell transplantation in these patients.

Therapeutic Intensification for HIV-associated Non-Hodgkin's Lymphoma by Autologous Transplantation of Either Unselected or CD34+-Selected Peripheral Blood Stem Cells, in Patients in First or Second Complete Remission. ANRS 131

Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:

Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation.

Secondary Outcome Measures:

Evaluation of:

HIV RNA

HIV DNA

Percentage and absolute count of CD3, CD4+ and CD8+ lymphocytes

Lymphocyte phenotypes and functions

TREC analysis

Immune reconstitution in vivo

Duration of aplasia

Enrollment:

1

Study Start Date:

February 2007

Study Completion Date:

October 2008

Primary Completion Date:

July 2008 (Final data collection date for primary outcome measure)

Detailed Description:

Highly active antiretroviral therapy (HAART) has dramatically reduced mortality and morbidity of HIV-infected patients by decreasing the incidence of opportunistic infections and HIV-related malignancies such as Kaposi sarcoma. However, the frequency of NHL remains increased in these patients. Moreover, their prognostic remains poor comparing to HIV negative patients. This is mainly due to the type of NHL (aggressive B, and frequent stage IV) but also host factors such as immunodeficiency, co-infections (EBV, HHV8), and chemotherapy-HAART interactions. In the lack of new and significantly more efficient treatments, therapeutic intensification such as high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), already tested in relapsed or partially responding HIV negative patients, could be an option in HAART controlled HIV+ patients with NHL, rather in first complete remission (CR) but with initially high International Prognosis Index (IPI above or equal to 2), or in second CR, whatever initial IPI. Positive selection CD34+ cells is an approach for depleting grafts of tumour cells and HIV DNA. However the delayed lymphocyte recovery following this process, may lead to increased incidence of opportunistic infections (OI) in HIV-infected patients. OI prophylaxis will be systematically associated.

Eligible patients will have peripheral blood stem cell (PBSC) mobilization and divided in two subgroups. Group A with 3-6 x 106 PBSC will not undergo CD34+ selection process and group B with more than 6 x 106 will undergo this process. The myeloablative conditioning process is the same in the two groups with total body irradiation before reinfusion of grafts.

Patients will be followed from week2 (W2) up to W60 with clinical and biological evaluations.

Eligibility

Ages Eligible for Study:

18 Years to 55 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

Adult patients between 18 and 55 years old at screening

Documented HIV-1 infection

Currently HAART-treated

Plasma HIV-RNA below 50 copies/ml at screening

Lymphocyte T CD4+ count above or equal to 100/mm3 at the NHL diagnosis

Histologically proven large cell NHL in first remission with classical poor prognostic factors (IPI above or equal to 2) or in second remission whatever IPI.

Biological criteria of eligibility for intensive therapeutic

Signed written informed consent

Patient protected by the social security of one of the European community countries.

Exclusion Criteria:

Burkitt NHL

Central nervous system NHL

Patients already treated by ASCT

Ongoing infectious disease

Psychiatric disease

Left ventricular ejection fraction < 25%

Creatinine clearance < 50 ml/min

Hepatic failure

Uncontrolled high blood pressure

Chronic hepatitis C or B

Participating in other trials.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00432419